Association of immunophenotype with expression of topoisomerase II α and β in adult acute myeloid leukemia

Sci Rep. 2020 Mar 26;10(1):5486. doi: 10.1038/s41598-020-62345-9.

Abstract

Anthracyclines used in the treatment of acute myelogenous leukemia (AML) inhibit the activity of the mammalian topoisomerase II (topo II) isoforms, topo II α and topo IIβ. In 230 patients with non-M3 AML who received frontline ara-C/daunorubicin we determined expression of topo IIα and topo IIβ by RT-PCR and its relationship to immunophenotype (IP) and outcomes. Treatment outcomes were analyzed by logistic or Cox regression. In 211 patients, available for analysis, topo IIα expression was significantly lower than topo IIβ (P < 0.0001). In contrast to topo IIα, topo IIβ was significantly associated with blast percentage in marrow or blood (P = 0.0001), CD7 (P = 0.01), CD14 (P < 0.0001) and CD54 (P < 0.0001). Event free survival was worse for CD56-negative compared to CD56-high (HR = 1.9, 95% CI [1.0-3.5], p = 0.04), and overall survival was worse for CD-15 low as compared to CD15-high (HR = 2.2, 95% CI [1.1-4.2], p = 0.02). Ingenuity pathway analysis indicated topo IIβ and immunophenotype markers in a network associated with cell-to-cell signaling, hematological system development/function and inflammatory response. Topo IIβ expression reflects disease biology of highly proliferative disease and distinct IP but does not appear to be an independent variable influencing outcome in adult AML patients treated with anthracycline-based therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism
  • Antineoplastic Agents / therapeutic use
  • Cohort Studies
  • Cytarabine / therapeutic use
  • DNA Topoisomerases, Type II / genetics
  • DNA Topoisomerases, Type II / metabolism*
  • Daunorubicin / therapeutic use
  • Female
  • Humans
  • Immunophenotyping
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / enzymology*
  • Leukemia, Myeloid, Acute / immunology*
  • Male
  • Middle Aged
  • Poly-ADP-Ribose Binding Proteins / genetics
  • Poly-ADP-Ribose Binding Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Topoisomerase II Inhibitors / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • Antigens, CD
  • Antineoplastic Agents
  • Poly-ADP-Ribose Binding Proteins
  • RNA, Messenger
  • Topoisomerase II Inhibitors
  • Cytarabine
  • DNA Topoisomerases, Type II
  • TOP2A protein, human
  • TOP2B protein, human
  • Daunorubicin